Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis

Autor: Zhe Liang, Mandy L. Ford, Nathan J. Klingensmith, Rohit Mittal, Lindsay M. Margoles, John D. Lyons, Maylene E. Wagener, Craig M. Coopersmith, Mara A. Serbanescu
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Glycosylation
Time Factors
Physiology
lcsh:Medicine
Lymphocyte Activation
Pathology and Laboratory Medicine
medicine.disease_cause
Memory T cells
Mice
White Blood Cells
T-Lymphocyte Subsets
Animal Cells
Immune Physiology
Medicine and Health Sciences
Cytotoxic T cell
lcsh:Science
Innate Immune System
Multidisciplinary
Organic Compounds
T Cells
Ingestion
Flow Cytometry
3. Good health
Chemistry
medicine.anatomical_structure
Physical Sciences
Cytokines
Tumor necrosis factor alpha
Cellular Types
Research Article
Immune Cells
T cell
Immunology
Cytotoxic T cells
Biology
Sepsis
03 medical and health sciences
Signs and Symptoms
Immune system
Diagnostic Medicine
Intensive care
medicine
Animals
Lymphocyte Count
Blood Cells
Ethanol
lcsh:R
Organic Chemistry
Chemical Compounds
Biology and Life Sciences
Cell Biology
Molecular Development
Immune dysregulation
medicine.disease
Disease Models
Animal
030104 developmental biology
Alcohols
Immune System
lcsh:Q
Physiological Processes
Immunologic Memory
Biomarkers
CD8
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 11, p e0165886 (2016)
ISSN: 1932-6203
Popis: Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.
Databáze: OpenAIRE
Externí odkaz: